Serum Proteins Predict Treatment-Related Cardiomyopathy Among Survivors of Childhood Cancer

IF 12 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Jacc: Cardiooncology Pub Date : 2025-01-01 DOI:10.1016/j.jaccao.2024.10.004

Suresh Poudel PhD , Him Shrestha PhD , Yue Pan PhD , Qian Li PhD , Kendrick Li PhD , Cindy Im PhD , Stephanie B. Dixon MD , Matthew J. Ehrhardt MD , Daniel A. Mulrooney MD , Suiping Zhou PhD , Haiyan Tan PhD , Anthony A. High PhD , Paul W. Burridge PhD , Smita Bhatia MD , John L. Jefferies MD , Kirsten K. Ness PhD , Melissa M. Hudson MD , Leslie L. Robison PhD , Gregory T. Armstrong MD , Junmin Peng PhD , Yadav Sapkota PhD

{"title":"Serum Proteins Predict Treatment-Related Cardiomyopathy Among Survivors of Childhood Cancer","authors":"Suresh Poudel PhD , Him Shrestha PhD , Yue Pan PhD , Qian Li PhD , Kendrick Li PhD , Cindy Im PhD , Stephanie B. Dixon MD , Matthew J. Ehrhardt MD , Daniel A. Mulrooney MD , Suiping Zhou PhD , Haiyan Tan PhD , Anthony A. High PhD , Paul W. Burridge PhD , Smita Bhatia MD , John L. Jefferies MD , Kirsten K. Ness PhD , Melissa M. Hudson MD , Leslie L. Robison PhD , Gregory T. Armstrong MD , Junmin Peng PhD , Yadav Sapkota PhD","doi":"10.1016/j.jaccao.2024.10.004","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Anthracyclines, a highly effective chemotherapy for many pediatric malignancies, cause cardiomyopathy, a major late effect in adult survivors. Biomarkers are needed for early detection and targeted interventions for anthracycline-associated cardiomyopathy.</div></div><div><h3>Objectives</h3><div>The aim of this study was to determine if serum proteins and/or metabolites in asymptomatic childhood cancer survivors can discriminate symptomatic cardiomyopathy.</div></div><div><h3>Methods</h3><div>Using an untargeted mass spectrometry–based approach, 867 proteins and 218 metabolites were profiled in serum samples of 75 asymptomatic survivors with subclinical cardiomyopathy and 75 individually matched survivors without cardiomyopathy from SJLIFE (St. Jude Lifetime Cohort Study). Models were developed on the basis of the most influential differentially expressed proteins and metabolites, using conditional logistic regression with a least absolute shrinkage and selection operator penalty. The best performing model was evaluated in 23 independent survivors with severe or symptomatic cardiomyopathy and 23 individually matched cardiomyopathy-free survivors.</div></div><div><h3>Results</h3><div>A 27-protein model identified using conditional logistic regression with a least absolute shrinkage and selection operator penalty discriminated symptomatic or severe cardiomyopathy requiring heart failure medications in independent survivors; 19 of 23 individually matched survivors with and without cardiomyopathy were correctly discriminated with 82.6% (95% CI: 71.4%-93.8%) accuracy. Pathway enrichment analysis revealed that the 27 proteins were enriched in various biological processes, many of which have been linked to anthracycline-related cardiomyopathy.</div></div><div><h3>Conclusions</h3><div>A risk model was developed on the basis of the differential expression of serum proteins in subclinical cardiomyopathy, which accurately discriminated the risk for severe cardiomyopathy in an independent, matched sample. Further assessment of these proteins as biomarkers of cardiomyopathy risk should be conducted in external larger cohorts and through prospective studies.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 1","pages":"Pages 56-67"},"PeriodicalIF":12.0000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782007/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Jacc: Cardiooncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666087324003582","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Anthracyclines, a highly effective chemotherapy for many pediatric malignancies, cause cardiomyopathy, a major late effect in adult survivors. Biomarkers are needed for early detection and targeted interventions for anthracycline-associated cardiomyopathy.

Objectives

The aim of this study was to determine if serum proteins and/or metabolites in asymptomatic childhood cancer survivors can discriminate symptomatic cardiomyopathy.

Methods

Using an untargeted mass spectrometry–based approach, 867 proteins and 218 metabolites were profiled in serum samples of 75 asymptomatic survivors with subclinical cardiomyopathy and 75 individually matched survivors without cardiomyopathy from SJLIFE (St. Jude Lifetime Cohort Study). Models were developed on the basis of the most influential differentially expressed proteins and metabolites, using conditional logistic regression with a least absolute shrinkage and selection operator penalty. The best performing model was evaluated in 23 independent survivors with severe or symptomatic cardiomyopathy and 23 individually matched cardiomyopathy-free survivors.

Results

A 27-protein model identified using conditional logistic regression with a least absolute shrinkage and selection operator penalty discriminated symptomatic or severe cardiomyopathy requiring heart failure medications in independent survivors; 19 of 23 individually matched survivors with and without cardiomyopathy were correctly discriminated with 82.6% (95% CI: 71.4%-93.8%) accuracy. Pathway enrichment analysis revealed that the 27 proteins were enriched in various biological processes, many of which have been linked to anthracycline-related cardiomyopathy.

Conclusions

A risk model was developed on the basis of the differential expression of serum proteins in subclinical cardiomyopathy, which accurately discriminated the risk for severe cardiomyopathy in an independent, matched sample. Further assessment of these proteins as biomarkers of cardiomyopathy risk should be conducted in external larger cohorts and through prospective studies.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Jacc: Cardiooncology Multiple-

CiteScore

12.50

自引率

6.30%

发文量

106

期刊介绍： JACC: CardioOncology is a specialized journal that belongs to the esteemed Journal of the American College of Cardiology (JACC) family. Its purpose is to enhance cardiovascular care for cancer patients by publishing high-quality, innovative scientific research and sharing evidence-based knowledge. The journal aims to revolutionize the field of cardio-oncology and actively involve and educate professionals in both cardiovascular and oncology fields. It covers a wide range of topics including pre-clinical, translational, and clinical research, as well as best practices in cardio-oncology. Key areas of focus include understanding disease mechanisms, utilizing in vitro and in vivo models, exploring novel and traditional therapeutics (across Phase I-IV trials), studying epidemiology, employing precision medicine, and investigating primary and secondary prevention. Amyloidosis, cardiovascular risk factors, heart failure, and vascular disease are some examples of the disease states that are of particular interest to the journal. However, it welcomes research on other relevant conditions as well.